Phosphonium Ionic Liquids as Recyclable Solvents for Solution Phase Chemistry

ABSTRACT

This application relates to the use of phosphonium-based ionic liquids as recyclable solvents for solution phase chemistry. The ionic liquids may be used, for example, as solvents for reactions involving Grignard reagents, hydridic reagents, metallic and non-metallic reducing agents, and strong bases, including nucleophilic carbenes and Wittig reagents. In one embodiment the invention may comprise homogeneous mixtures of strong bases/nucleophiles/reducing agents and tetrahydrocarbylphosphonium salt ionic liquids. The invention also relates to chemical processes that may proceed in either minimally flammable solvent, or a complete absence of flammable solvent, including systems containing strong reducing agents such as alkali and alkaline metals or metal and non-metal hydrides. Methods for generating anions and nucleophililic carbenes (imidazol-2-ylidenes) (and complexes derived from them) in phosphonium-based ionic liquids are also described. The invention demonstrates the feasibility of using phosphonium-based ionic liquids as a reliable reaction media for a wide variety of basic reagents. The problems associated with C—H activation in imidazolium-based ionic liquids by highly reactive bases are not observed for phosphonium-based ionic liquids.

REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of U.S. provisional patentapplication Ser. No. 60/588,318 filed 16 Jul. 2004, which is herebyincorporated by reference.

FIELD OF THE INVENTION

This application relates to the use of ionic liquid solvents forsolution phase chemistry.

BACKGROUND OF THE INVENTION

Environmental pressure to reduce waste and re-use materials has promptedstudies into “Green” chemistry.^(1,2) Various reports have reviewedthese emerging fields^(3,4,5) and it is apparent that one of the mostdifficult areas to make environmentally friendlier is solution phasechemistry. Solvents play key roles in chemical reactions; they serve tohomogenize and mix reactants, and also act as a heat sink for exothermicprocesses. It is clear that one of the biggest industrial concerns isreplacement of volatile organic compounds (VOCs),⁶ particularly thosethat are toxic, such as CH₂Cl₂, and those that are hazardous to handle.Of the latter class of VOCs, the most offensive are ethers, which arevolatile, flammable, and form explosive peroxides. Unfortunately,ethereal solvents are commonly used for reactions involving strongbases⁶ and few alternatives are currently available.

Successful attempts to replace or limit the use of VOCs have been madein some cases, and these include processes that use no solvent⁷ or newsolvent systems such as supercritical H₂O^(8,9,10) supercritical CO₂,¹¹fluorous solvents,¹² and ionic liquids (ILs).^(2,13,14)

Perhaps the most extensively studied class of ILs is based upon theimidazolium ion, 1, and the most common example is theethylmethylimidazolium ion with anions such as [BF₄] and [AlCl₄].¹⁵

Notwithstanding the sensitivity of the anions, ILs of this class havegarnered attention since they facilitate many important chemicalreactions. Solutions of IL 1 support reactions such as alkeneoligomerizations, alkylations,¹⁶ and acylations.¹⁷ However,imidazolium-based solvent systems are unsuitable for reactions involvingeither active metals (i.e., Na or K) or in reactions that involve strongbases (i.e. Grignards, organolithiums, and amides) since these reagentsreact with the imidazolium-based solvents. For instance, imidazoliumions react with potassium metal to produce imidazol-2-ylidenes(N-heterocyclic carbenes, NHCs),¹⁸ and treatment of imidazolium ionswith bases, such as lithium di-iso-propylamide or potassiumtert-butoxide, is the standard method for the generation of NHCs.¹⁹Aggarwal et al. have shown that even with weaker bases, such as amines,low reported yields from the Baylis-Hillman reaction in animidazolium-based ionic liquid were the result of addition of thedeprotonated imidazolium cation to an aldehyde.²⁰ Finally, the other“Greener” solvent alternatives, namely H₂O^(8,21,22) and supercriticalCO₂,¹¹ react with strong bases.

Dupont et al. have recognized that under certain reaction conditions,both the cation and the anion of imidazolium-based ionic liquids mayundergo undesirable transformations.²³ Accordingly, some caution must beexercised when using imidazolium-based ionic liquids as solvents. Forexample, as explained above, when such ILs are employed under basicconditions, carbenes are likely to form with possibly detrimentalresults. Under reduction conditions in an electrochemical cellimidazolium-based ionic liquids also decompose.²⁴ Simple alkylation ofthe 2-position of the imidazolium ion does not prevent unfavorabledeprotonation and redox chemistry, as was shown by the deprotonation ofthe substituted pentamethylimidazolium ion, which produces an ylidicolefin, 1,3,4,5-tetramethyl-2-methyleneimidazoline.²⁵ Other ions used inionic liquids also undergo unfavorable chemistry with reducing agents.For example, pyridinium-based ionic liquids react with reducing agentsor in an electrochemical cell to produce highly colored dimericmaterials.^(26.27) Some of these materials are based upon the generalstructure of viologen, among the most carcinogenic compounds known.

The use of phosphonium-based (PILs) rather than imidazolium-based ionicliquids as solvents is also known in the prior art. Canadian patentapplication No. 2,356,709, which was laid open for public inspection on3 Mar. 2003, describes the use of tetrahydrocarbylphosphonium salt ionicliquids as solvents for dissolving saturated hydrocarbons. The '709application describes how reaction products can be separated from theionic liquid by the addition of water, resulting in the formation ofseparate liquid phases.

United States patent application No. 2004/0106823 published 3 Jun. 2004describes various phosphonium phosphinate compounds useful as ionicliquids. Such compounds may be used as polar solvents for use inchemical reactions, such as Michael additions, aryl coupling,Diels-Alder, alkylation, biphasic catalysis, Heck reactions,hydrogenation or some enzymatic reactions.

It is also well known that phosphonium ions are more thermally robustthan ammonium ions.

Although phosphonium and ammonium ions have been used in nucleophilicreaction chemistry, specifically with the alkylation of2-naphthoxide,^(29,30) the anion in that application is not very basic(pKa≈10).³¹ The use of phosphonium-based ionic liquids as solvents forGrignard reagents and other strong bases and nucleophiles has not beenpreviously described in the prior art. As shown in FIG. 1, Grignardreagents are organomagnesium halides having the general formula RMgXthat are commonly used in synthetic chemistry and are highlybasic.^(32,33) For example, Grignard reagents can be used in thesynthesis of alcohols and carboxylic acids. While non-aqueous etherealsolvents are commonly used in Grignard chemistry, the inventors havedetermined that Grignard reagents and other strong bases are alsopersistent and reactive in phosphonium-based ionic liquids. Further,some basic compounds, such as nucleophilic carbenes, can be generated inthe phosphonium-based ionic liquids. Surprisingly, highly basic ornucleophilic reagents do not result in appreciable deprotonation ofphosphonium-based ionic liquids to form phosphoranes. Thus the presentinvention demonstrates the feasibility of replacing volatile andflammable solvents typically used for Grignard chemistry and the likewith more environmentally friendly and recyclable alternatives. Theinvention also demonstrates the usefulness of phosphonium-based ionicliquids as reliable solvents in which to produce strongly basicnucleophiles, such as nucleophilic carbenes, and also to dissolve andhandle highly reactive molecules such as borane (BH₃).

SUMMARY OF THE INVENTION

In accordance with the invention, a stable homogenous mixture isprovided comprising a recyclable phosphonium-based ionic liquid solventhaving the general formula I wherein R₁, R₂, R₃ and R₄ are each ahydrocarbyl or substituted hydrocarbyl moiety and X is an anion.

The mixture further comprises a reagent dissolved in the solvent,wherein the reagent is selected from the group consisting of a strongbase, a reducing agent and a nucleophile.

In one embodiment R₁, R₂, R₃ and R₄ are each independently an alkylgroup, a cycloalkyl group, an alkenyl group, an alkynyl group and anaryl group. The substituted hydrocarbyl moiety may possess a heteroatom(e.g. O, S, N, etc). The anion may be selected from the group consistingof halides, phosphinates, alkylphosphinates, alkylthiophosphinates,sulphonates, amides, tosylates, aluminates, borates, arsenates,cuprates, sulfates, nitrates, carboxylates, acetate, decanoate, citrateand tartrate.

In various particular embodiments of the invention the solvent isselected from the group consisting of trihexyl(tetradecyl) phosphoniumchloride, trihexyl(tetradecyl) phosphonium decanoate,tripentyl(tetradecyl) phosphonium chloride, trioctyl(tetradecyl)phosphonium chloride, trihexyl(tetradecyl) phosphonium bromide,trihexyl(tetradecyl) phosphonium bis (trifluoromethylsulfonyl)imide,trihexyl(tetradecyl) phosphonium dicyclohexyl-phosphinate,trihexyl(tetradecyl) phosphonium tetrafluoroborate, trihexyl(tetradecyl)phosphonium triflate, trihexyl(tetradecyl) phosphoniumtris(trifluoromethylsulfonyl)imide, trihexyl(tetradecyl) phosphoniumtris(trifluoromethylsulfonyl)methide, andtriisobutyl(tetradecyl)(methyl) phosphonium tosylate.

In one embodiment, the solvent is a purified solution substantially freeof water. The solvent in the mixture may contain a relatively lowconcentration of ethereal solvent or may be substantially free ofethereal solvent. The mixture may also comprise a co-solvent selectedfrom the group consisting of tetrahydrofuran, benzene, toluene andrelated solvents.

The reagent may be a Grignard reagent in one embodiment of theinvention. In another embodiment, the reagent is a hydridic reagent. Thehydridic reagent is selected from the group consisting of BH₃ or NaBH₄or a substituted borane. The reagent may also comprise a carbene, ametal such as K or a metal amalgam.

The invention also relates to the use of the mixture described above toperform chemical reactions. The use may comprise, for example, adding areactant to the mixture, such as an organic or organometallic compound.In one embodiment the reactant is a metal and the mixture furthercomprises of an imidazolium-based material.

The invention also relates to a method of using a phosphonium-basedionic liquid (PILs) for solution phase chemistry comprising providing aphosphonium-based ionic liquid solvent having the general structure (I)as described above; dissolving a reagent in the solvent to form areagent solution, wherein the reagent is selected from the groupconsisting of a strong base, a reducing agent and a nucleophile; andusing the reagent solution to perform a chemical reaction.

The method may comprise purifying the solvent prior to dissolving thereagent therein. The method may also include the step of recycling thesolvent for reuse after the chemical reaction. The chemical reaction maycomprise reacting the reagent with a reactant introduced into saidsolvent. The chemical reaction may, for example, be a reduction, anaddition or a basic catalytic reaction. In some embodiments the reagentmay be a Grignard reagent, a hydridic reagent, a metal, a metal amalgamor a nucleophilic carbene. The reactant may include an organic or anorganometallic compound.

The chemical reaction may produce one or more organic or organometallicproducts, and the method may further include the steps of isolating theproducts from the solvent. The products may be isolated in a liquidphase layer separate from the solvent. The invention also encompassesproducts derived from the applicant's method.

BRIEF DESCRIPTION OF THE DRAWINGS

In drawings, which describe embodiments of the invention but which,should not be considered as restricting the spirit or scope of theinvention in any way.

FIG. 1 is a scheme showing reaction of a Grignard reagent, C₆H₅MgBr intrihexyl(tetradecyl) phosphonium chloride under different reactionconditions, namely (i) DMF, (ii) NaBH₄, (iii) acetone, (iv)benzaldehyde, (v) 2,6-dibromo-iodobenzene, (vi) Br₂ and (vii) CuCl₂. Allreactions were followed by an aqueous work-up and an extraction withhexanes.

FIG. 2 is a photograph showing the separation of a solution mixture intoa three-phase system with the organic layer on the top, thephosphonium-based ionic liquid in the middle and the aqueous layer onthe bottom.

FIG. 3 is a space filling MM2 molecular model diagram of the structureof 1,3-bis(2,4,6-trimethylphenyl) imidazolium cation.

FIG. 4 is a space filling MM2 molecular model of the structure oftrihexyl(tetradecyl) phosphonium cation showing the acidic C—H sitesurrounded by non-rigid alkyl groups.

FIG. 5 shows chemical structures of 1,3-bis(diethyl) imidazolium (left)and tetraethylphosphonium (right) ions examined in computationalstudies.

FIG. 6 shows estimated Mullikan partial charges on the 1,3-bis (diethyl)imidazolium and tetraethylphosphonium ions of FIG. 5.

DETAILED DESCRIPTION OF THE INVENTION

Throughout the following description specific details are set forth inorder to provide a more thorough understanding of the invention.However, the invention may be practiced without these particulars. Inother instances, well known elements have not been shown or described indetail to avoid unnecessarily obscuring the present invention.Accordingly, the specification and drawings are to be regarded in anillustrative, rather than a restrictive, sense.

Defined Terms

The current invention relates to the use of phosphonium-based ionicliquids (PILs) as recyclable solvents for solution phase chemistry. Asused herein, the terms “phosphonium-based ionic liquids” and “PILs”means liquids having the following general formula (I) where R₁, R₂, R₃and R₄ are each a hydrocarbyl or substituted hydrocarbyl moiety and X isany anion.

As used herein the term “hydrocarbyl” means a hydrocarbon radical havingonly carbon and hydrogen atoms and the term “substituted hydrocarbyl”means a hydrocarbyl radical wherein one or more, but not all, of thehydrogen and/or the carbon atoms are substituted, for example replacedby a halogen, nitrogen, oxygen, sulfur or phosphorus atom or a radicalincluding a halogen, nitrogen, oxygen, sulfur or phosphorus atom, e.g.fluoro, chloro, cyano, nitro, hydroxyl, phosphate, thiol, etc. Thus thesubstituted hydrocarbyl moiety may possess, for example, a heteroatom(e.g. O, S, N, etc).

The term “PIL reaction media” as used herein refers to the combinationof a PIL solvent and one or more reagents. As will be apparent from thedetailed description below, PIL solvents may serve as a valuable carrierfor various reactive and synthetically valuable reagents. For example,the reaction media may comprise a Grignard reagent dissolved in a PILsolvent. The reaction media may also optionally include otherco-solvents, such as THF, hexanes or toluene. The reaction media can becombined with a reactant to perform a chemical reaction to produce oneor more reaction products. As shown in FIG. 1, examples of reactantsreactive with Grignard reagents include DMF, NaBH₄, benzaldehyde,dibromoiodobenzene, Br₂ and CuCl₂.

Formation and Use of Reaction Media

The PIL solvents of the present invention may be formed from a broadrange of phosphonium cations and a broad range of anions. As explainedabove, such solvents include phosphonium salts that have the generalformula [PR₄]⁺[X]⁻ where R is independently a hydrocarbyl or substitutedhydrocarbyl moiety and X is any anion. Suitable anions include, forexample, halides, phosphinates, alkylphosphinates,alkylthiophosphinates, sulphonates, amides, tosylates, aluminates,borates, arsenates, cuprates, sulfates, nitrates, carboxylates, acetate,decanoate, citrate and tartrate. By way of further example, suitable PILsolvents may be selected from the group consisting oftrihexyl(tetradecyl) phosphonium chloride, trihexyl(tetradecyl)phosphonium decanoate, tripentyl(tetradecyl) phosphonium chloride,trioctyl(tetradecyl) phosphonium chloride, trihexyl(tetradecyl)phosphonium bromide, trihexyl(tetradecyl) phosphonium bis(trifluoromethylsulfonyl)imide, trihexyl(tetradecyl) phosphoniumdicyclohexylphosphinate, trihexyl(tetradecyl) phosphoniumtetrafluoroborate, trihexyl(tetradecyl) phosphonium triflate,trihexyl(tetradecyl) phosphonium tris(trifluoromethylsulfonyl)imide,trihexyl(tetradecyl) phosphonium tris(trifluoromethylsulfonyl)methide,and triisobutyl(tetradecyl)(methyl) phosphonium tosylate.

One of the most readily available and affordable PILs istrihexyl(tetradecyl) phosphonium chloride which is available from CytecCanada Inc (CYPHOS® IL 101). Whereas the trihexyl(tetradecyl)phosphonium cation is available with numerous other anions, some ofwhich have favourable properties such as lower viscosity and donorsolvent abilities, they are often somewhat more expensive since they areoften prepared from trihexyl(tetradecyl) phosphonium chloride via ionexchange reactions. While commercially produced. PILs, specificallyCYPHOS® IL 101 (trihexyl(tetradecyl) phosphonium chloride) are availablein high purity, these ionic liquids typically contain traces of residualphosphines, HCl or other acidic species, and water. Due to thesensitivity of many basic reagents, such as organometallic or hydridicmolecules, purification of PILs is desirable. In accordance with theinvention, any excess HCl or other acidic species in the PILs isneutralized by aqueous sodium hydrogen carbonate. Care should be takensince there can be excessive foaming in this step. The ionic liquidlayer is then washed vigorously with water and extracted using hexanes.For the organometallic reactions described below, it is important toremove all traces of water. The PILs can be dried by azeotropicdistillation with toluene or benzene. Optionally, they can also befurther dried at this stage with a small amount of solid potassiummetal. It is noteworthy that the PILs do not react with elementalpotassium (which in theory is the source of the simplest base, theelectron).

Reaction media comprising PILs are suitable for a broad class ofreactants and/or reaction types. For example, one or more of thefollowing basic reagents may be dissolved in the PIL solvent to form apersistent and homogenous reaction media:

1. Grignard reagents

2. Hydrides commonly BH₃ and NaBH₄

3. Phenoxides

4. Alkoxides

5. Acetylides

6. Amides

7. Metallic reducing agents such as sodium or potassium

8. Non-metallic reducing agents, such as dithionite

9. Wittig reagents, such as Ph₃P═CH₂

10. Carbenes, such as N-heterocyclic carbenes

The reaction media may then be combined with one or more reactants toform the target product(s).

As will be appreciated by a person skilled in the art, the order inwhich the solvent, reagent and reactant are combined is sometimes notnecessarily critical. For example, in some cases the reactant may firstbe combined with the PIL solvent and the reagent (such as a Grignardreagent) may then be added to the mixture to perform a chemicalreaction. After the desired chemical reaction, further steps may beperformed to isolate the desired reaction product and/or recycle thesolvent for further use.

By way of further illustration, the desired reactions may be performedin several manners, including:

-   -   1. The basic reagent (e.g. a reagent from items 1-10 above) is        mixed with the PIL solvent and the reactant is then added,        either neat or in solution, or    -   2. The reactant is mixed with the PIL solvent and the reagent        (in solution, or neat) is then added to the mixture.

After the reaction, the product(s) can be isolated either by extractionor by distillation/sublimation. For example, the PIL can be reclaimedand recycled after reaction either by:

-   -   1. Addition of water followed by extraction of the product using        an organic solvent. After several extraction and water washes,        the PIL can be warmed to drive off volatiles, dried, and reused;        or    -   2. The product can be distilled from the PIL, and the PIL washed        with water and organic solvent, if necessary, to remove any        salts/organics.        As shown in FIG. 2, after the desired chemical reaction is        performed, the addition of water and hexanes to the reaction mix        results in the formation of a three-phase system, with the        organic layer on the top, ionic liquid in the middle, and the        aqueous layer on the bottom. As explained above, in some other        cases the product can be distilled directly from the        phosphonium-based ionic liquid.

Comparison of PILs and IILs

PIL solvents and reaction media have different chemical characteristicsthan more conventional imidazolium-based ionic liquids (IILs). WhileIILs have been known to support many reactions that proceed well in whatcan be considered to be acidic reaction conditions^(16,17,34) the trackrecord for IILs to support reactions involving strong bases isconsiderably less favourable.^(20,21) The most common problemencountered by IILs in basic conditions is deprotonation of the C—H siteas shown in Scheme 1.

As shown in Scheme 1, carbenes (A) are neutral molecules possessingdicoordinated carbon atom with two non-bonding electrons. They are sixelectron species and accordingly very reactive.³⁵ N-heterocycliccarbenes (NHCs) are of particular interest due to their numerousapplications in synthetic chemistry.^(19,36) NHCs are highly basic andare strong donor ligands with poor π-acceptor characteristics. Thisclass of ligand has been extensively used in transition metal chemistryas shown in the structure below to stabilize low³⁷ and, more recently,high oxidation state metal complexes.³⁸ Access to these importantspecies as a “free” (or uncomplexed) reagent in an IL would beparticularly advantageous.

Organometallic chemistry in ILs is dominated by the formation ofmetal-carbene complexes and has heretofore focused primarily on IILs.For example, organometallic reagents¹⁴ have been used in ILs, and newmetal carbonyl complexes have been incorporated into ILS.³⁹ Allylationreactions using tetraallylstannane, indium and tin as catalyst^(40,41)have also been reported. Synthesis and use of zinc reagents fororganometallic reaction in ILs have also been carried out.^(42,43)However, the use of ILs as reaction media for free or uncomplexedcarbenes has not been extensively investigated. NHCs and other basessuch as phosphines dissolved in ILs could have numerous potentialapplications in catalysis including the cyclotrimerization ofisocyanates,⁴⁴ generation of homoenolates,⁴⁵ organocatalytic livingpolymerization,46 ring-opening polymerization of cyclic esters⁴⁷ andcarbon-carbon bond formation reactions.⁴⁸ Metal-carbene complexes arehighly reactive in a wide variety of useful organic reaction types;however, their formation in ionic liquids nevertheless shows one of themajor downfalls of IILs since the acidic C—H bond in the imidazoliumions is extremely reactive, both in acid-base chemistry as well as redoxchemistry. In some catalytic reactions, this deprotonation reaction canbe of great use and importance^(49,50,51) (i.e., it generates an activemetal/NHC complex), but in other cases, such as in the Baylis-Hillmanreaction (Scheme 2A), deprotonation reactions (Scheme 2B) results in asignificant decrease in reaction yields.²⁰

In this application the inventors demonstrate that PILs appear to bemore robust than IILs and can be used as solvents for Grignardreactions⁵² and for dissolving other carbon centred ligands amongothers. Moreover, PILs can be used as solvents for dissolving NHCs andfor a number of unexpected applications namely, generating NHCs, and forpreparing metal complexes of the NHCs.

As described in the Examples below, there appears to be steric reasonswhy deprotonation reactions occur more in imidazolium-based ionicliquids than in phosphonium-based ionic liquids. The imidazolium ring ismore rigid whereas the alkyl chains on the phosphonium ions are flexibleand thus provide more protection to the reactive proton. As shown in thespace filling diagrams of the relevant molecules, namely1,3-bis(2,4,6-trimethylphenyl) imidazolium ion (FIG. 3) andtrihexyl(tetradecyl) phosphonium ion (FIG. 4), it is very difficult tosterically shield the carbeneic site in the imidazolium ion, whereas inthe trihexyl(tetradecyl) phosphonium ion there is considerable stericcongestion and flexibility and hence access to the reactive C—H site isdiminished. Electronic factors may also contribute to make the PILs moreresistant to reduction than IILs.

The inertness of PILs (e.g. CYPHOS® IL 101) towards reaction with basestherefore appears to have primarily a kinetic basis. Although it wouldbe reasonable to expect that deprotonation of a phosphonium ion toproduce phosphorane and a salt would be thermodynamically favored,evidence of this reaction has not been observed. Contrast this withWittig reagents, which are derived from materials analogous to PILs(CYPHOS® IL 101), but generally with significantly shorter alkylgroups.^(×) Access to the reactive protic site on CYPHOS® IL 101 isdifficult and hence the Grignard reagents dissolve in the CYPHOS® IL 101but fail to react with the phosphonium component. Further support forthis kinetic argument is provided by noting that [Ph₃PCH₂CH₃]⁺[Br]⁻ isdeprotonated to form a phosphorane by CYPHOS® IL 103/PhMgBr solutions orother bases such as potassium tert-butoxide as shown by ³¹P{¹H} NMRstudies. These solutions exhibit a single signal at 15 ppm, consistentwith the presence of Ph₃P═CH(CH₃),53 and also consistent with anoriginal sample dissolved in the phosphonium ionic liquid.

Persistence and Stability of Reagents in PILs

Perhaps the most readily available carbon-based nucleophiles arecommercial solutions of Grignard reagents in tetrahydrofuran. As arepresentative example of this important class of reagent isphenylmagnesium bromide (PhMgBr) in PIL. As demonstrated in the Examplesbelow, anhydrous samples of CYPHOS® IL 101 form clear solutions with lowviscosity when mixed with commercially available 1M PhMgBr intetrahydrofuran.^(↑) The solutions are air and moisture sensitive, butcan be stored under an inert atmosphere. Most importantly, deprotonationof the PIL CYPHOS® IL 101 to produce a phosphorane has not beenobserved.

Addition of anhydrous bromine to fresh solutions of PIL CYPHOS® IL101/Grignard reagent resulted in the exclusive formation of PhBr.Further, 5% of biphenyl was detected when the one-month-old PIL CYPHOS®IL 101/Grignard reagent solution was quenched with Br₂. For these agedsolutions, the presence of benzene was not observed, again consistentwith no deprotonation of the PIL CYPHOS® IL 101. However, completeremoval of THF from the PIL CYPHOS® IL 101/Grignard solutions results inthe formation of biphenyl and a variety of products that can be tracedto the decomposition of the PIL CYPHOS® IL 101, includingtetradecyl(dihexyl)phosphine and hexene. Electron transfer can explainthis result from the Grignard reagent to the PILs CYPHOS® IL 101. Forreactivity studies the best results were obtained when the ratio ofTHF:PIL CYPHOS® IL 101 was 1:3.

Ether free Grignard solutions in phosphonium-based ionic liquids werealso synthesized using trihexyl(tetradecyl) phosphonium decanoate asdetailed in the Examples below. To the phosphonium-based ionic liquid, afew drops of THF was added and the solution was cooled to −78° C. and toit Grignard reagents dissolved in THF was added and allowed to stir atroom temperature for 15 minutes. THF was removed in vacuo to yield anether free Grignard solution that was stable over a month.

Reactivity of Grignard and Other Reagents in PILs

As detailed in the Examples below, a survey of chemical reactions wasperformed to determine the reactivity of Grignard reagents in PILsincluding addition to carbonyl compounds (i, ii, iii), benzyne reactions(iv), halogenation (v) and coupling reactions (vi) (FIG. 1).

After the reaction of the electrophile and the Grignard reagent at roomtemperature, addition of water and hexanes to the reaction mixtureresult in the formation of a three-phase system (FIG. 2), with theorganic layer on the top, ionic liquid in the middle and the aqueouslayer on the bottom. An added benefit for this system is the high heatcapacity of PIL and therefore it is not necessary to cool the reactionsolutions to the extremely low temperatures often needed for etherealsolutions. The products were isolated from the organic layer andanalyzed by Gas-Chromatography Mass Spectrometry (GC-MS). In some cases,the low yields reported in FIG. 1 reflect the partitioning between theionic liquid and the organic phase. Isolated yields can be markedlyimproved by successive extractions. In some cases, due to the highthermal stability of the PILs and the volatility of the products,distillation-could be used to remove the product from the reactionmixtures. In all cases, the PIL (e.g. CYPHOS® IL 101) can be washed withwater and hexanes, dried, and re-used.

As explained above, some of the most basic neutral ligands are thecarbenes with pK_(a) values in the range of 22 to 24.^(54,24) They havebeen used extensively in transition metal-based catalysis and they havebeen shown to be key ligands in a number of very important syntheticprocedures. Highly basic solutions containing NHCs dissolved in PILs canbe prepared by mixing the carbene with the phosphonium-based ionicliquid, followed by addition of several drops of benzene, or toluene toreduce viscosity, if necessary. The addition of the co-solventfacilitates dissolution and after dissolution, the co-solvent can beremoved under vacuum with no effect on the stability of the remainingsolution. Other strong neutral bases, such as triphenylphosphine, havebeen examined and have been found to be similarly persistent in PILs asshown by spectroscopic studies.

Generations and Reactions of NHCs in PILs

The inventors have shown that imidazolium ions could be converted tonucleophilic carbenes by their treatment with metallic potassium¹⁸ andhave concurrently noted that PILs do not react with potassium metalunder the conditions described. Thus, treatment of1,3-bis(2,4,6-trimethyl)phenylimidazolium chloride suspended in PILswith potassium results in the formation of1,3-bis(2,4,6-trimethyl)phenylimidazol-2-ylidene. It was also noted thatwhen 1,3-bis(2,4,6-trimethyl-phenyl) imidazolium chloride in CYPHOS® IL101 was treated with PhMgBr, the corresponding NHC was obtained furtherconfirming that the reactive C—H site is more accessible in the IIL thanin the PIL. This compound is unambiguously assigned by the observationof the ¹³C NMR for the carbeneic carbon≈216 ppm, as well as throughreactivity studies (see below). The solutions are highly viscous andlight brown in color. Likewise, these highly basic solutions are stablein excess of one month and are active for organic transformations, forexample treatment of 1,3-bis(2,4,6-trimethyl)phenylimidazol-2-ylidene inPIL catalyses the condensation of benzaldehyde (benzoin condensation)with a yield of 40%.

The inventors have surveyed the chemistry of NHCs in PILs through anexamination of some well-established NHC chemistry. The products werecharacterized exclusively in PIL using techniques such as NMR, IR andMass spectroscopy (MS), GC-MS and elemental analysis. The NHC solutionsprepared in CYPHOS® IL 101 behave as normal carbene solutions as shownin Scheme 3. Two representative examples from the p-block⁵⁶ and thed-block transition metals were chosen to illustrate the reactivity ofNHCs in PIL. Treatment of the NHC with S₈ produces the thione asindicated by ¹³C NMR spectroscopy and mass spectrometry. Diagnostic peakof the thione in MS (CI) occurs at 336.3. These data are consistent tothat previously reported for IMes=S.⁵⁷ NHCs coordinated to transitionmetal site have attracted interest in catalysis and we illustrate thereactivity of NHC in CYPHOS® IL 101 by reacting the solution withCr(CO)₆. Displacement of one carbonyl occurs to afford IMesCr(CO)₅ asidentified in IR studies.

Generation of Highly Basic Phosphoranes (Wittig Reagents) and their usein Ionic Liquids

Synthetically, one of the most valuable classes of C-based nucleophilesare the phosphoranes, also known as Wittig reagents.³³ These moleculesreact readily with aldehydes and ketones to produce C═C double bonds,from which other valuable reactions proceed. Wittig reagents range fromweakly basic, ‘stabilized ylides’ (pKa of the conjugate acid ca. 8-11)to highly basic derivatives (pKa of [Ph₃P—CH₃] ca. 22.5 in DMSO). Use ofstabilized derivatives have been reported in IILs, but generation of theylides and especially the highly basic ones, has not been reported. Theability of PILs to be inert with respect to reactions with many basesmakes these attractive reagents to be prepared. A general reactionscheme for a Wittig reaction is shown in Scheme 4 below.

Generation of Wittig reagents is possible in PILs. For example,[Ph₃PCH₂CH₃]⁺[Br]⁻ is deprotonated to form a phosphorane by CYPHOS® IL103/PhMgBr solutions or other bases such as potassium tert-butoxide asshown by ³¹P{¹H} NMR studies. The phosphorane obtained by deprotonationof [Ph₃PCH₂CH₃]⁺[Br]⁻ has a distinctive ³¹P{¹H} peak at 15 ppmconsistent with the phosphorane dissolved in CYPHOS® IL 103. Theresulting ylide is synthetically useful, and can be used in the Wittigreaction with aldehydes and ketones to generate an alkene as shown inthe Examples section. The by-product of a Wittig reaction istriphenylphosphine oxide, and after reaction a white residue wasisolated and characterized by mass spectrometry which exhibited a majorpeak at 278 amu.

Catalytic C—C Bond Forming Reactions using Grignard Reagents in PILs

Up to now, we have primarily highlighted stoichiometric reactionsinvolving Grignard reagents, although other reactions are possible. Forexample, catalytic C—C bond forming reactions using Grignard reagentsare possible. Low valent transition metal complexes generated in situcan also act as a catalyst for C—C bond formation in PILs. Typically,such metal species react with IILs through oxidation addition reactionsto the metal producing carbene complexes of the metal, and this caneither be a positive or negative reaction for the metal sites. In PILsthe low valent metal sites maintain their reactivity and behave asexpected. For example, the Kumada-Corriu cross-coupling reactionproceeds well in PIL trihexyl(tetradecyl) phosphonium decanoate. The lowvalent nickel complex catalyst can be generated in situ by treatment ofNi(Cod)₂ (Cod=cyclooctadiene) and the free NHC1,3-di(2,6-diisopropylphenyl)imidazol-2-ylidene and its reactivity isconfirmed by the coupling of ether free solutions of PhMgBr intrihexyl(tetradecyl) phosphonium decanoate with the 4-halotoluene(halo=F, Cl, Br, I) as shown in Scheme 5 below.⁵⁸ Related aminationreactions also proceed well and an example is provided in the Examplessection.

Finally, borane (BH₃) forms stable solutions with phosphonium ionicliquids. These are new materials that are highly efficient, odorless,non-volatile, nonflammable, and reusable reagents for borane transferreactions. The hydride component of BH₃ does not react with thephosphonium cation and hence the PIL is a useful carrier of thisversatile reagent. The inventors have demonstrated their utility in anumber of carbonyl reduction reactions. These new materials should bepotentially useful carriers of this highly reactive molecule for a widevariety of applications, especially in organic synthesis as well as,possibly, in fuel delivery systems, noting the potential importance ofBorane as a hydrogen carrier. More experimental details are provided inthe Examples section.

EXAMPLES

The following examples will further illustrate the invention in greaterdetail although it will be appreciated that the invention is not limitedto the specific examples.

1. General Procedure

Gas Chromatography Mass Spectrometry (GC-MS) was carried out on theextracts using Gas Chromatography Electron Ionisation detector G 1800AGCD system. Distillation was carried out using a standard Kulgelröhrapparatus. Reported yields were determined by gas chromatography using,where possible, reference materials, and the yields is determined byintegration. In some cases, the yields reported are isolated yields.Standard techniques such as NMR infrared spectroscopy in combinationwith and elemental analysis were used to characterize reaction mixturesand products.

Purification of the phosphonium-based ionic liquids is important and arepresentative procedure is described here: Saturated sodium hydrogencarbonate (20 ml) was added to trihexyl(tetradecyl) phosphonium chlorideor trihexyl(tetradecyl) phosphonium decanoate (120 mL) and stirred for15 minutes. Vigorous foaming occurred. The solution was then washed withwater (3×500 mL). The ionic liquid layer obtained was then extractedwith hexanes (120 mL) and water (120 mL) in 3×40 mL aliquots. The ionicliquid was then dried by azeotropic distillation using toluene (20 mL),followed by exhaustive evacuation. ¹H NMR spectroscopy showed theabsence of water in the ionic liquid and ³¹P NMR spectroscopy showed thepresence of only one type of phosphorus site and no residual phosphinespresent. The dried ionic liquid can be stored in the presence ofmetallic potassium, which helps to maintain the anhydrous nature of thesystem.

2. Reaction of Phenylmagnesium Bromide with Dimethylformamide inTrihexyl(tetradecyl) Phosphonium Chloride

To dried ionic liquid trihexyl(tetradecyl) phosphonium chloride (15 mL),CYPHOS® IL 101, was added commercially available phenylmagnesium bromidesolution in tetrahydrofuran (5.00 mL, 5.00 mmol). To itN,N′-dimethyl-formamide (0.37 g, 5.00 mmol) was added drop-wise and thesolution was stirred under nitrogen for 3 hours. The reaction mixturewas then quenched with saturated ammonium chloride followed by water. Asingle extraction step was performed as follows: Hexanes were added toform a three-phase system and the benzaldehyde was extracted in thehexanes layer. The hexanes layer was dried with anhydrous magnesiumsulphate and filtered off. The extract was analyzed by GC-MS giving a55% yield of benzaldehyde.

3. Reduction of Benzaldehyde with Sodium Borohydride inTrihexyl(tetradecyl) Phosphonium Chloride

To dried trihexyl(tetradecyl) phosphonium chloride (15 mL) (CYPHOS® IL101), benzaldehyde (1.0 g, 9.41 mmol) was added. To this solution anexcess of sodium borohydride (0.43 g, 11.46 mmol) was added and allowedto stir for 3 hours. The reaction mixture was then quenched withsaturated ammonium chloride followed by water and hexanes to form athree-phase system. Hexanes extract was dried using anhydrous magnesiumsulphate and filtered off. Both the hexanes layer and the ionic liquidlayer were analyzed by GC-MS to give a 60% yield of benzyl alcohol.

4. Reaction of Phenylmagnesium Bromide with Acetone inTrihexyl(tetradecyl) Phosphonium Chloride

To dried ionic liquid trihexyl(tetradecyl) phosphonium chloride (15 mL),1 M phenylmagnesium bromide solution in tetrahydrofuran (5.00 mL, 5.00mmol) was added. To this stirred solution acetone (0.29 g, 5.00 mmol)was added dropwise and allowed to stir for 3 hours and quenched undernitrogen with saturated ammonium chloride followed by water. Hexaneswere added to extract 2-phenyl-propan-2-ol and the hexanes extract afterdrying with anhydrous magnesium sulphate and ionic liquid layer wereanalyzed by GC-MS giving a total yield of 82%. Distillation under vacuumwas also carried out giving a yield of 75%.

5. Reaction of 2,4,6-trimethylphenylmanesium Bromide with Benzaldehydein Trihexyl(tetradecyl) Phosphonium Chloride

To dried ionic liquid trihexyl(tetradecyl) phosphonium chloride (15 mL),1 M 2,4,6-trimethylphenylmagnesium bromide solution in tetrahydrofuran(2.80 mL, 2.80 mmol) was added and to it benzaldehyde (0.30 g, 2.80mmol) was added dropwise and the mixture was stirred for 3 hours. Thereaction mixture was then quenched with saturated ammonium chloride andwater followed by hexanes. The ionic liquid layer was pumped to removeany trace of hexanes. The product was then removed from the ionic liquidusing distillation giving a 50% yield ofphenyl-(2,4,6-trimethyl-phenyl)-methanol.

6. Preparation of Stock Solutions of Ethereal Grignards inTrihexyl(tetradecyl) Phosphonium Chloride or Trihexyl(tetradecyl)Phosphonium Decanoate

Stock solutions of reaction media comprising Grignard reagents inphosphonium ionic liquids were prepared by mixing commercially availableethereal (i.e. in diethyl ether, tetrahydrofuran, etc.) solutions ofGrignard reagents with phosphonium ionic liquids cooled at −78° C.Ethereal solutions of Grignard reagents dissolved intrihexyl(tetradecyl) phosphonium chloride or trihexyl(tetradecyl)phosphonium decanoate are air and moisture sensitive. These solutionsshow no significant sign of degradation after one month as shown byreactivity studies.

7. Generation of an Ether Free Solution Composed of a Grignard ReagentDissolved in an Ionic Liquid

To trihexyl(tetradecyl)phosphonium decanoate (5 mL) with a few drops ofTHF (up to 1 mL), commercially available 1M phenylmagnesium bromide (5.0mL) in THF was added at −78° C. The mixture was stirred and warmed toroom temperature. Tetrahydrofuran was removed in vacuo leaving a viscouspale yellow or orange solution to which hexanes (2.0 mL) was added toreduce viscosity. Treatment of this solution with either bromine orN,N′-dimethylformamide followed by quenching with saturated aqueousammonium chloride and addition of water followed by extraction withdichloromethane resulted in the formation of bromobenzene (98%) andbenzaldehyde (99%), respectively, as determined by GC-MS studies.

8. Chemical Reaction Involving Potassium Metal in Phosphonium-basedIonic Liquids: Generation of an NHC in a PIL

1,3-bis(2,4,6-trimethylphenyl) imidazolium chloride (2.00 g, 5.87 mmol)and an excess of potassium metal (0.35 g, 8.75 mmol), previously washedwith anhydrous THF, were added to trihexyl(tetradecyl) phosphoniumchloride (10 mL). The reaction mixture was heated at 80° C. undernitrogen for 24 hours. Hexanes (10 ml) were added to the resultingsuspension and the solution was filtered through Celite to removeundissolved materials. Evacuation to remove hexanes gave a brown viscousresidue that was characterized as a solution of trihexyl(tetradecyl)phosphonium chloride and1,3-bis(2,4,6-trimethylphenyl)-imidazol-2-ylidene. ¹H NMR (THF-d₈, 400MHz): δ 2.08 (s, 2,6-CH₃, 12H), 2.31 (s, 4-CH₃, 6H), 6.96 (s, ArH, 4H),7.14 (s, NCH, 2H); ¹³C NMR (THF-d₈, 101 MHz) 18.6 (s, 2,6-CH₃), 21.6 (s,4-CH₃), 122.1 (s, NCC), 129.8 (s, Mes C-3,5), 136.2 (s, Mes C-2,6),138.2 (s, Mes C-4), 139.9 (s, Mes C-1), 215.8 (s, NCN). Thesespectroscopic data are consistent with an original sample of1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene dissolved intrihexyl(tetradecyl) phosphonium chloride.

9. Wittig Reactions: Formation of Methylstyrene in Phosphonium-basedIonic Liquids

To a cold (−78° C.) sample of trihexyl(tetradecyl) phosphonium decanoate(5 mL), 1 M phenylmagnesium bromide in THF (1.2 mL, 1.2 mmol) was addedand allowed to slowly warm to room temperature. The THF was removedunder vacuum, and to the resulting solution hexanes (approximately 2 mL)was added to reduce viscosity. Triphenylethylphosphonium bromide (0.4 g,1.10 mmol) was then added to the solution. A color change from white toreddish orange was observed and the mixture was stirred under nitrogenfor 1 hour. ³¹P{¹H} NMR showed a distinctive peak at 15.3 ppm for thedeprotonation of triphenylethylphosphonium bromide to give thephosphorane. Benzaldehyde (0.11 g, 1.10 mmol) was then added to themixture and an instant colour change from yellow to white was observed.The mixture was allowed to stir for 2 hours and then quenched withwater. The product was extracted with dichloromethane which was driedusing anhydrous magnesium sulphate to give methylstyrene (96%) analyzedby GC-MS. The presence of Ph₃PO was confirmed by mass spectrometry.

10. Formation of N-heterocyclic Carbenes in phosphonium-based IonicLiquids

1,3-bis(2,4,6-trimethylphenyl)imidazolium chloride (0.25 g, 100% ¹³Clabeled at C2) and a solution composed of ether free PhMgBr (2.00 mmol)dissolved in trihexyl(tetradecyl) phosphonium decanoate (5 mL) weremixed at room temperature. A small amount of toluene was added to reducethe viscosity and to facilitate stirring. NMR studies on the reactionmixtures show the presence of a major peak in the ¹³C NMR spectrum at218 ppm, consistent with the formation of 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene.

1,3-bis(2,4,6-trimethylphenyl) imidazolium chloride (2.00 g, 5.87 mmol)and an excess of potassium metal (0.35 g, 8.75 mmol), previously washedwith anhydrous THF, were added to trihexyl(tetradecyl) phosphoniumchloride (15 mL). The reaction mixture was heated at 80° C. undernitrogen for 24 hours. Hexanes (10 mL) were added to the resultingsuspension and the solution was filtered through Celite. Evacuation toremove hexanes gave a reddish brown viscous material, and this residuewas characterized as a solution of trihexyl(tetradecyl) phosphoniumchloride and 1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene. ¹H NR(THF-d₈, 400 MHz): δ 2.08 (s, 2,6-CH₃, 12H), 2.31 (s, 4-CH₃, 6H), 6.96(s, ArH, 4H), 7.14 (s, NCH, 2H); ¹³C NMR (THF-d₈, 101 MHz) 18.6 (s,2,6-CH₃), 21.6 (s, 4-CH₃), 122.1 (s, NCC), 129.8 (s, Mes C-3,5), 136.2(s, Mes C-2,6), 138.2 (s, Mes C-4), 139.9 (s, Mes C-1), 215.8 (s, NCN).These spectroscopic data are consistent with1,3-bis(2,4,6-trimethylphenyl) imidazol-2-ylidene dissolved intrihexyl(tetradecyl) phosphonium chloride.

11. Use of Hydridic Reagents in Phosphonium-based Ionic Liquids

A stable compound having the general empirical formulatrihexyl(tetradecyl) phosphonium chloride.BH₃ (1a.BH₃) ortrihexyl(tetradecyl)-phosphonium decanoate.BH₃ (2a.BH₃) can be preparedby either passing gaseous B₂H₆ through samples of the pure ionic liquidsor by addition of one equivalent of BH₃.THF solution followed bycomplete removal of the THF by exhaustive evacuation. Solutions of anyratio (e.g. 1-100%) of BH₃ to ionic liquid can be prepared. We have usedthese new ionic liquids (i.e. reaction media) for classic reductionsinvolving borane, namely reduction of the carbonyl function. A series ofreactions were performed by combining stoichiometric amounts (based onhydride) of carbonyl compounds with the new phosphonium-based ionicliquids at room temperature. Yields were determined by gaschromatography mass spectrometry analysis (GC-MS) of the extracts. Thedata are presented in chart 1 below.

CHART 1 PIL · BH₃ Reactant Product Yield (%) 1a · BH₃ BenzyldehydeBenzyl alcohol 94% 2a · BH₃ Benzyldehyde Benzyl alcohol 95% 1a · BH₃Benzoyl chloride Benzyl alcohol 90% 2a · BH₃ Benzoyl chloride Benzylalcohol 99% 1a · BH₃ Benzophenone Benzhydrol 60% 2a · BH₃ BenzophenoneBenzhydrol 99% 1a · BH₃ Cinnamaldehyde Cinnamyl alcohol 75% 2a · BH₃Cinnamaldehyde Cinnamyl alcohol 61% 1a · 10% BH₃ Benzaldehyde Benzylalcohol 80% 2a · 10% BH₃ Benzaldehyde Benzyl alcohol 91%Spectroscopic data for the new borane containing materials: ¹H NMR(C₆D₆)of complex 1a.BH₃: δ 2.7-0.8 (various m); ³¹P NMR(C₆D₆) δ 33.5; ¹¹B NMRof 1a.BH₃ (C₆D₆) showed a very broad signal ca. 50 to −25 ppm with sharpfeatures at 18.6 ppm, −12.0 ppm and a sharp quintet at −35.3 ppmassigned to BH₄ ⁻; IR (neat): 2956 (s), 2924 (s), 2855 (s), 2037 (m),2212 (m), 2298 (s), 1465 (s), 1416 (s), 1378 (m), 1337 (s), 1261 (m),1215 (m), 1166 (m), 1115 (s), 1071 (m), 814 (s), 721 (s) cm⁻¹; Anal.Calcd for C₃₂H₇₁BClP: C, 72.09; H, 13.42. Found: C, 72.39; H, 13.64. ¹HNMR(C₆D₆) of 2a.BH₃: an upfield shift of the ¹H NMR, δ 2.6-0.8 (variousm); ³¹P NMR(C₆D₆) δ3.4; ¹¹B NMR of 2a.BH₃ (C₆D₆) showed a very broadpeak ca. δ 50 to −25 ppm with sharp resonances at δ 18.1 ppm, 2.1 ppmand a very sharp quintet at −35.3 ppm assigned to BH₄ ⁻; IR (neat): 2956(s), 2925 (s), 2855 (s), 2139 (m), 2224 (m), 2270 (s), 1661(s) (C═Ostretch of 2a.BH₃ complex), 1579 (m) (C═O stretch of uncomplexed 2a),1466 (s), 1416 (s), 1378 (m), 1337 (s), 1297 (m), 1150 (m), 1111 (m),1075 (m), 720 (m), 669 (s).12. Kumada-Corriu Cross-coupling Reaction with Ni Catalyst inPhosphonium-based Ionic Liquid

A stock solution of 1.0 M PhMgBr in THF (5 mL, 5 mmol) was added to coldIL 103 (5.0 mL) at −78° C. The reaction mixture warmed up to roomtemperature and the THF was removed in vacuo. To it toluene (0.5 mL) wasadded to reduce viscosity, followed by the addition of one equivalent(wrt PhMgBr) of 4-fluorotoluene, 4-chlorotoluene, 4-bromotoluene or4-iodotoluene. To this solution, 0.05 mol percent of the complexbis[1,3-di(2′,6′-diisopropylphenyl)imidazolin-2-ylidene]nickel (O),prepared in situ by the reaction of nickel dicyclooctadiene and the freeN-heterocyclic carbene in IL 103, was added. On addition of nickeldicyclooctadiene to N-heterocyclic carbene a color change from paleyellow to dark green was observed. The reaction mixture was stirred for18 hours at room temperature under nitrogen and then quenched with a fewdrops of methanol and extraction was carried out using dichloromethaneand water. The dichloromethane layer was then dried using anhydrousmagnesium sulphate and then analysed by GC-MS. Yields are tabulated inChart 2 below. In all cases a small amount (<2%) of biphenyl wasobserved.

CHART 2 Yield of 4- Yield of 4,4′-Dimethyl- Reagent 1 Reagent 2phenyltoluene biphenyl 4-fluorotoluene PhMgBr 42% 0% 4-chlorotoluenePhMgBr 88% 0% 4-bromotolene PhMgBr 73% 25% 4-iodotoluene PhMgBr 74% 22%

13. Synthesis of a Phenoxide in a Phosphonium-based Ionic Liquid and itsReactivity

Phenol (0.2 g, 2.13 mmol) was added to IL 103 (5.0 mL) followed bytoluene (0.5 mL) to reduce viscosity. Potassium metal previously washedwith THF (0.12 g, 3.19 mmol) was added to the reaction mixture and itwas heated at 80° C. for 3 hours under nitrogen. A white precipitateformed. The excess potassium metal was removed and one equivalent ofbenzoyl chloride was added and the mixture was heated at 80° C. for 2hours. No color change was observed. The reaction mixture was thenquenched with water and extracted with dichloromethane. The extractswere dried with anhydrous magnesium sulphate and analyzed by GC-MS andthe data was consistent with a 91% yield of phenyl benzoate.

14. Reaction of Magnesium Acetylides in Phosphonium-based Ionic Liquids

To trihexyl(tetradecyl) phosphonium decanoate (5 mL), commerciallyavailable 1M ethynylmagnesium bromide (5.0 mL) in THF was added at −78°C. The mixture was stirred and warmed to room temperature.Tetrahydrofuran was removed in vacuo leaving a viscous brown solution towhich toluene (1 mL) was added to reduce viscosity. To this solution oneequivalent of cyclohexanone was added and it was stirred for 16 hoursunder nitrogen. The reaction mixture was then quenched with water andthen extracted with dichloromethane which was analysed by GC-MS afterdrying with anhydrous magnesium sulphate to give a 78% yield of1-ethynyl-cyclohexanol.

To trihexyl(tetradecyl) phosphonium decanoate (5 mL) commerciallyavailable 1M phenylethynylmagnesium bromide (5.0 mL) in THF was added at−78° C. The mixture was stirred and warmed to room temperature.Tetrahydrofuran was removed in vacuo leaving a viscous brown solution towhich toluene (1 mL) was added to reduce viscosity. To this solution oneequivalent of benzaldehyde was added and it was allowed to stir for 16hours under nitrogen. The reaction mixture was then quenched with waterand then extracted with dichloromethane which was analysed by GC-MSafter drying with anhydrous magnesium sulphate to give a 82% yield of1,3-diphenyl-prop-2-yn-1-ol.

15. Reaction of Amides in Phosphonium-based Ionic Liquid

To trihexyl(tetradecyl) phosphonium decanoate (5 mL), commerciallyavailable 1M phenylmagnesium bromide (5.0 mL) in THF was added at −78°C. The mixture was stirred and warmed to room temperature.Tetrahydrofuran was removed in vacuo leaving a viscous orange solutionto which toluene (1 mL) was added to reduce viscosity. Morpholine (0.44g, 5.05 mmol) was added dropwise followed by 0.05 mol % of the complexbis[1,3-di(2′,6′-diisopropylphenyl)imidazolin-2-ylidene]nickel (O),prepared in situ by the reaction of nickel dicyclooctadiene and the freeN-heterocyclic carbene in IL 103. A color change from orange to brownwas observed. To the reaction mixture one equivalent (wrt morpholine) of4-chlorotoluene was added and the solution was stirred for 16 hoursunder nitrogen at 85° C. The mixture was cooled to room temperature andthe mixture quenched with the addition of a few drops of methanol andwater and extracted using dichloromethane. The dichloromethane layer wasthen dried using anhydrous magnesium sulphate and analyzed by GC-MSgiving 58% yield of 4-p-tolyl-morpholine.

To trihexyl(tetradecyl) phosphonium decanoate (5 mL), potassiumtert-butoxide (0.85 g, 7.5 mmol) was added followed by toluene (1 mL)reduce viscosity. Morpholine (0.44 g, 5.05 mmol) was added dropwisefollowed addition of 0.05 mol % of the complexbis[1,3-di(2′,6′-diisopropylphenyl)imidazolin-2-ylidene]nickel (O),prepared in situ by the reaction of nickel dicyclooctadiene and the freeN-heterocyclic carbene in IL 103. A color change from white to brown wasobserved. To the reaction mixture one equivalent (wrt morpholine) of4-chlorotoluene was added and the solution was stirred for 16 hoursunder nitrogen at 85° C. The mixture was cooled to room temperature andthe mixture quenched with the addition of a few drops of methanol andwater and extracted using dichloromethane. The dichloromethane layer wasthen dried using anhydrous magnesium sulphate and analyzed by GC-MSgiving 55% yield of 4-p-tolyl-morpholine.

16. Reaction of a Non-metallic Reducing Agent in Phosphonium-based IonicLiquid

To trihexyl(tetradecyl) phosphonium decanoate (5 mL), iodine (ca. 0.2 g)was added. A dark red brown solution was obtained and to it sodiumbisulphite was added with a few drops of water to increase solubitly ofsodium bisulphate (excess). Decolorization from dark brown to paleyellow occurs without decomposition of the ionic liquid as confirmed bygas chromatography mass spectrometry.

17. Computational Studies

A study of symmetrically substituted imidazolium and phosphonium ions(FIG. 5) was performed to examine the partial charges in thealpha-protons in the relevant ions. All calculations were performed withthe Gaussian 98 package of programs and the geometry was optimized atthe UB3LYP/6-31G level and partial atom charges were calculated usingthe UB3LYP/6-311G*(2df,p) method.⁵⁹ The partial atom charges for thecenters of interest and the results are shown in FIG. 6.

The structural parameters calculated for both the imidazolium⁶⁰ andphosphonium ions⁶¹ are comparable to those observed by X-raycrystallography. The estimated partial charges on the reactive C—Hfragments, which are the potential points at which strong bases caninteract with the cationic species, are of particular interest. As shownin FIG. 6, there are slightly greater charges on the reactive C—H sitesin the imidazolium ion case, compared to the analogous sites in thephosphonium case.

Based solely on these results it is not clear why deprotonationreactions occur so readily for the imidazolium-based systems rather thanthe phosphonium ions. As discussed above, it is believed that theimidazolium ring is more rigid whereas the alkyl chains on thephosphonium ions are flexible and thus provide more protection to thereactive proton. As shown in the space filling diagrams on relevantmolecules namely 1,3-bis(2,4,6-trimethylphenyl) imidazolium ion andtrihexyl(tetradecyl) phosphonium ion (FIGS. 3 and 4), it is verydifficult to sterically shield the carbeneic site in the imidazoliumion, whereas in the actual trihexyl(tetradecyl) phosphonium ion there isconsiderable steric congestion and flexibility and hence access to thereactive C—H site is diminished.

As will be apparent to those skilled in the art in the light of theforegoing disclosure, many alterations and modifications are possible inthe practice of this invention without departing from the spirit andscope thereof. Accordingly, the scope of the invention is to beconsidered in accordance with the substance defined by the followingclaims:

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1. A stable homogenous mixture comprising a recyclable phosphonium-basedionic liquid solvent having the general formula I.

wherein R₁, R₂, R₃ and R₄ is independently a hydrocarbyl or substitutedhydrocarbyl moiety and X is an anion; and a reagent dissolved in saidsolvent, wherein said reagent is selected from the group consisting of astrong base, a reducing agent and a nucleophile.
 2. The mixture asdefined in claim 1, wherein R₁, R₂, R₃ and R₄ is independently an alkylgroup, a cycloalkyl group, an alkenyl group, an alkynyl group, or anaryl group.
 3. The mixture as defined in claim 1, wherein said anion isselected from the group consisting of halides, phosphinates,alkylphosphinates, alkylthiophosphinates, sulphonates, amides,tosylates, aluminates, borates, arsenates, cuprates, sulfates, nitrates,carboxylates, acetate, decanoate, citrate and tartrate.
 4. The mixtureas defined in claim 1, wherein said solvent is selected from the groupconsisting of: trihexyl(tetradecyl) phosphonium chloride,trihexyl(tetradecyl) phosphonium decanoate, tripentyl(tetradecyl)phosphonium chloride, trioctyl(tetradecyl) phosphonium chloride,trihexyl(tetradecyl) phosphonium bromide, trihexyl(tetradecyl)phosphonium bis(trifluoromethylsulfonyl)imide, trihexyl(tetradecyl)phosphonium dicyclohexylphosphinate, trihexyl(tetradecyl) phosphoniumtetrafluoroborate, trihexyl(tetradecyl) phosphonium triflate,trihexyl(tetradecyl) phosphonium tris(trifluoromethylsulfonyl)imide,trihexyl(tetradecyl) phosphonium tris(trifluoromethylsulfonyl)methide,and triisobutyl(tetradecyl)(methyl) phosphonium tosylate.
 5. The mixtureas defined in claim 1, wherein said solvent is trihexyl(tetradecyl)phosphonium chloride or trihexyl(tetradecyl) phosphonium decanoate 6.The mixture as defined in claim 1, wherein said solvent is anhydrous ornearly anhydrous.
 7. The mixture as defined in claim 1, wherein saidsolvent is a purified solution and is substantially free of water. 8.The mixture as defined in claim 7, wherein said purified solution issubstantially free of acidic species.
 9. The mixture as defined in claim1, wherein said mixture is substantially free of ethereal solvent. 10.The mixture as defined in claim 1, wherein said reagent is a Grignardreagent.
 11. The mixture as defined in claim 1, wherein said reagent isa hydridic reagent.
 12. The mixture as defined in claim 11, wherein saidhydridic reagent is selected from the group consisting of BH₃, NaBH₄, asubstituted borane and transitional metal or non-metal hydrides.
 13. Themixture as defined in claim 1, wherein said reagent is selected from thegroup consisting of a nucleophilic carbene, a Wittig reagent, aphosphorane and a C-based nucleophile.
 14. The mixture as defined inclaim 1, wherein said reagent is a metal or a metal amalgam.
 15. Themixture as defined in claim 1, further comprising a co-solvent selectedfrom the group consisting of tetrahydrofuran, benzene, toluene, diethylether and a poly-ether.
 16. Use of the mixture defined in claim 1, toperform chemical reactions.
 17. Use as defined in claim 16, comprisingadding a reactant to said mixture.
 18. Use as defined in claim 17,wherein said reactant is an organic or organometallic compound.
 19. Useas defined in claim 16, wherein said chemical reaction is selected fromthe group consisting of a reduction, an addition and a basic catalyticreaction.
 20. Use as defined in claim 16, wherein said reactant is ametal and said mixture further comprises an imidazolium-based ionicliquid or an imidazolium ion.
 21. A method of using a phosphonium-basedionic liquid for solution phase chemistry comprising: (a) providing aphosphonium-based ionic liquid solvent having the general structure (I)as defined in claim 1 above; (b) dissolving a reagent in said solvent toform a reagent solution, wherein said reagent is selected from the groupconsisting of a strong base, a reducing agent and a nucleophile; and (c)using said reagent solution to perform a chemical reaction.
 22. Themethod as defined in claim 21, comprising purifying said solvent priorto dissolving said reagent therein.
 23. The method as defined in claim22, where said purifying comprises removing any water present in saidsolvent.
 24. The method as defined in claim 22, wherein said purifyingcomprises neutralizing any acidic species present in said solvent. 25.The method as defined in claim 21, further comprising recycling saidsolvent for reuse after said chemical reaction.
 26. The method asdefined in claim 21, wherein said chemical reaction is performed at roomtemperature.
 27. The method as defined in claim 21, wherein saidchemical reaction comprises reacting said reagent with a reactantintroduced into said solvent.
 28. The method as defined in claim 21,wherein said chemical reaction is selected from the group consisting ofa reduction, an addition and a basic catalytic reaction.
 29. The methodas defined in claim 21, wherein said reagent is a Grignard reagent. 30.The method as defined in claim 21, wherein said reagent is a hydridicreagent.
 31. The method as defined in claim 21, wherein said reagent isa metal or metal amalgam.
 32. The method as defined in claim 21, whereinsaid reagent is selected from the group consisting of a nucleophiliccarbine, a Wittig reagent, a phosphorane, a C-based nucleophile and a P-or S-ylide.
 33. The method as defined in claim 27, wherein said reactantis an organic or organometallic compound.
 34. The method as defined inclaim 21, wherein said chemical reaction produces one or more organic ororganometallic products, and wherein said method further comprisesisolating said products from said solvent.
 35. The method as defined inclaim 34, wherein said products are isolated in a liquid phase layerseparate from said solvent.
 36. A product derived from the methoddefined in claim
 21. 37. A method of synthesizing a nucleophilic carbenecomprising reacting an imidazolium ion source with a metal in an organicliquid solvent.
 38. The method as defined in claim 37, wherein saidsolvent is selected from the group consisting of a phosphonium ionicliquid and an ethereal solvent.
 39. The method as defined in claim 37,wherein said imidazolium ion source is an imidazolium based ionicliquid.
 40. The method as defined in claim 37, wherein said metal ismetallic potassium.
 41. A method of using a phosphonium-based ionicliquid for solution phase chemistry comprising: (a) providing aphosphonium-based ionic liquid solvent having the general structure (I)as defined in claim 1 above; (b) dissolving a Grignard reagent in saidsolvent to form a reagent solution; and (c) using said reagent solutionto perform a chemical reaction.